ERK phosphorylation: Spatial and temporal regulation by G protein-coupled receptors

G protein-coupled receptors (GPCRs) are a major target in the drug discovery process. One important response that results from activation of a wide range of GPCRs is activation of the ERK signalling cascade. Given the abundance of both upstream activators and downstream targets of ERK1/2, the precise spatiotemporal control of ERK1/2 phosphorylation is crucial for maintaining the specificity of the physiological outcome. ERK activity is regulated via a number of mechanisms including compartmentalisation and scaffolding proteins. These scaffolding proteins can enhance the transduction of a specific signalling pathway by targeting pathway components to particular intracellular locations or signalling complexes. Recently, a number of fluorescent indicators of ERK1/2 phosphorylation have been developed that allow the regulation of this pathway to be investigated with greater spatiotemporal resolution than was previously possible. These fluorescent probes in conjunction with those for other signalling cascades should help unravel the spatiotemporal organisation of this pathway.